Structural modifications leading to changes in supramolecular aggregation of thiazolo[3, 2-a]pyrimidines: Insights into their conformational features

Abstract

The compounds, 7-methyl-3,5-diphenyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (1), 3-amino-2-cyano-7-methyl-5-phenyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl ester (2), 2-dimethylaminomethylene-7-methyl-3-oxo-5-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (3), 2-(3-cyano-benzylidene)-5-(4-hydroxy-phenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl ester; with N,N-dimethyl-formamide (4) and 3-ethoxycarbonylmethyl-5-(4-hydroxy-3-methoxy-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl ester (5) have been synthesized and their structures evaluated crystallographically. Compound 1 crystallizes in the space group Pı̄ with Z=8, with four molecules in the asymmetric unit. Compound 2 also crystallizes in the space group Pı̄ with Z=4 wherein asymmetric unit accommodates two molecules. Compound 3 belongs to P2₁/c with Z=4, compound 4 crystallizes in Pbc2 ₁ with Z=4 and compound 5 belongs to Pı̄ with Z=2. In all the above compounds, the aryl ring positioned at C5 of thiazolopyrimidine ring is almost perpendicular. In the case of compounds with substituted phenyl ring, aryl group-up conformation predominates. However, for compounds with unsubstituted phenyl ring, aryl group-down conformation is adopted. By varying the substituents at positions C2, C3, C6 and on the aryl at C5 in the main molecular scaffold of (1-5), we have observed significant differences in the intermolecular interaction patterns. The packing features of the compounds are controlled by C-H…O, C-H…N, N-H…N O-H…N, C-H…π and π…π weak interactions.